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Biomedical subjects

Christian G Kohler

Publications and source records attributed to Christian G Kohler.

15 recordsLinked to original sources

Schizophrenia Spectrum Biomarkers Consortium: Establishment of a Biorepository for the Discovery of Quantitative Fluid Biomarkers.

BACKGROUND AND HYPOTHESIS: Schizophrenia spectrum disorders (SSDs) produce severe symptoms, disability, and premature mortality, but only partially effective symptomatic treatments exist. Treatment development is impeded by lack of insight into disease mechanisms or objective biomarkers for clinical trials. Advances in genetics and neurobiology have converged on strong pathogenic hypotheses for SSDs centered on synapse dysfunction and excessive pruning, pathogenic processes that may produce measurable proteomic evidence in cerebrospinal fluid (CSF). Leveraging design precedents from successful fluid biomarkers discovery for Alzheimer's disease, we undertook a pilot study to test the feasibility of repeated CSF and blood samples collection from individuals with SSDs. Here we report on successful implementation of longitudinal bio-behavioral phenotyping in SSDs and establishment of a repository to permit broad sample and data sharing. STUDY DESIGN: The Schizophrenia Spectrum Biomarkers Consortium (SSBC) study principles included longitudinal study design, paired CSF and plasma collection associated with robust phenotypic characterization, at 3 academic sites and the establishment of a biorepository. Participants underwent clinical and cognitive assessments, neuroimaging, blood draws, and CSF collection via lumbar puncture (LP) every 6 months. STUDY RESULTS: SSBC successfully enrolled 48 SSD and 41 Healthy Controls with a 73% longitudinal retention. Clinical, cognitive, and neuroimaging results were consistent across sites and with existing studies. Study procedures were well tolerated, and almost all LPs (99%) resulted in either no or minor headache/backache that resolved without medical interventions. CONCLUSIONS: The pilot SSBC study demonstrates that a multi-site, longitudinal study with repeat CSF collection is feasible, with excellent participant acceptability and retention.

Humans↗

Phenylthiocarbamide (PTC) perception in patients with schizophrenia and first-degree family members: relationship to clinical symptomatology and psychophysical olfactory performance.

The inability to taste phenylthiocarbamide (PTC; "taste-blindness") has been associated with a number of medical and neurological illnesses not typically related to taste. We examined PTC sensitivity in 67 schizophrenia patients, 30 healthy controls, and 30 first-degree relatives to determine whether taster status could represent a simple vulnerability marker. A higher prevalence of non-tasters was seen in patients and family members relative to healthy controls. Among patients, non-tasters exhibited increased levels of negative and first-rank symptoms as well as poorer right nostril odor identification skills relative to PTC tasters. These differences were not explained by age, sex, education, smoking, or intensity differences. Phenotypic variation in PTC sensitivity is thought to be genetic in origin and suggests greater illness risk for those subjects with recessive taster alleles.

Adult↗

Gender differences in facial emotion recognition in persons with chronic schizophrenia.

BACKGROUND: The aim of the present study was to investigate possible sex differences in the recognition of facial expressions of emotion and to investigate the pattern of classification errors in schizophrenic males and females. Such an approach provides an opportunity to inspect the degree to which males and females differ in perceiving and interpreting the different emotions displayed to them and to analyze which emotions are most susceptible to recognition errors. METHODS: Fifty six chronically hospitalized schizophrenic patients (38 men and 18 women) completed the Penn Emotion Recognition Test (ER40), a computerized emotion discrimination test presenting 40 color photographs of evoked happy, sad, anger, fear expressions and neutral expressions balanced for poser gender and ethnicity. RESULTS: We found a significant sex difference in the patterns of error rates in the Penn Emotion Recognition Test. Neutral faces were more commonly mistaken as angry in schizophrenic men, whereas schizophrenic women misinterpreted neutral faces more frequently as sad. Moreover, female faces were better recognized overall, but fear was better recognized in same gender photographs, whereas anger was better recognized in different gender photographs. CONCLUSIONS: The findings of the present study lend support to the notion that sex differences in aggressive behavior could be related to a cognitive style characterized by hostile attributions to neutral faces in schizophrenic men.

Adult↗

Flat affect in schizophrenia: relation to emotion processing and neurocognitive measures.

Impaired emotional functioning in schizophrenia is a prominent clinical feature that manifests primarily as flat affect. Studies have examined the perception, experience, and expression of emotions in schizophrenia and reported normal ratings of experience but impaired affect identification. However, the relation between flat affect and performance on facial affect identification and cognitive tasks has not been systematically examined in relation to premorbid adjustment and clinical outcome. We report a prospective study of 63 patients with at least moderate severity of flat affect and 99 patients without flat affect, who were compared on functional domains, emotion processing tasks, and neurocognitive measures. Flat affect was more common in men and was associated with poorer premorbid adjustment, worse current quality of life, and worse outcome at 1-year follow-up. Patients overall performed more poorly on emotion processing tasks, one that required identification of happy and sad emotions and one that required differentiating among intensities within these emotions. They responded inaccurately yet faster than controls for the intensity differentiation task, suggesting a decomposition of the normal relation between accuracy and speed. Flat affect ratings, compared with other negative symptoms, uniquely predicted performance on emotion processing tasks. Patients with flat affect showed greater impairment in both emotion processing tasks, with the most pronounced impairment for the intensity differentiation task. However, the 2 patient groups did not differ in the neurocognitive profile except for verbal memory. We conclude that flat affect is an important clinical feature of schizophrenia that exacerbates the course of illness.

Adolescent↗

Olfactory functioning in schizophrenia: relationship to clinical, neuropsychological, and volumetric MRI measures.

Deficits in odor identification and detection threshold sensitivity have been observed in schizophrenia but their relationship to clinical, cognitive, and biologic measures have not been clearly established. Our objectives were to examine the relationship between measures of odor identification and detection threshold sensitivity and clinical, neuropsychological, and anatomic brain measures. Twenty-one patients with schizophrenia and 20 healthy controls were administered psychophysical tests of odor identification and detection threshold sensitivity to phenyl ethyl alcohol. In addition, clinical symptom ratings, neuropsychological measures of frontal and temporal lobe function and whole brain MRIs were concurrently obtained. Patients exhibited significant deficits in odor identification but normal detection threshold sensitivity. Poorer odor identification scores were associated with longer duration of illness, increased negative and disorganized symptoms, and the deficit syndrome, as well as impairments in verbal and nonverbal memory. Better odor detection thresholds were specifically associated with first-rank or productive symptoms. Larger left temporal lobe volumes with MRI were associated with better odor identification in controls but not in patients. Given the relevance of the neural substrate, and the evidence of performance deficits, psychophysical probes of the integrity of the olfactory system hold special promise for illuminating aspects of the neurobiology underlying schizophrenia.

Adult↗

Prognostic variables at intake and long-term level of function in schizophrenia.

OBJECTIVE: This study assessed the relationship between symptoms and cognitive measures at intake and functional outcome 2-8 years later (average 3 years) in first-episode and previously treated schizophrenia patients. METHOD: A composite cognitive score was assessed at intake to determine the influence of cognition on later functional outcome. At intake and follow-up, positive and negative symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms, and affective symptoms were assessed with the Hamilton Depression Rating Scale. Level of function in seven domains (social function, occupational function, independent living, symptom severity, fullness of life, extent of psychiatric hospitalization, and overall level of function) at intake and follow-up was assessed with the Strauss-Carpenter Level of Function scale. The contributions of sex, education, and duration of illness to functional outcome were also examined. RESULTS: The results indicated that symptoms at intake had distinct patterns of prognostic significance for functional outcome in previously treated patients, compared with first-episode patients. In addition, male and female patients differed in the degree to which initial symptoms were correlated with later function. CONCLUSIONS: Initial level of function, symptoms, sex, education, and duration of illness are all important predictors for functional outcome in patients with schizophrenia.

Activities of Daily Living↗

Apolipoprotein E genotype and odor identification in schizophrenia.

The authors examined Apolipoprotein E (ApoE) genotype frequencies and unirhinal odor identification in 28 schizophrenia patients and 26 healthy comparison subjects. No significant associations between ApoE status and olfaction were observed in either diagnostic group. The authors concluded that olfactory deficits in schizophrenia do not appear to be mediated by the ApoE allele.

Adult↗

Emotion-discrimination deficits in mild Alzheimer disease.

OBJECTIVE: Mild Alzheimer disease (AD) preferentially affects temporal lobe regions, which represent important structures in memory and emotional processes. This study investigated emotion discrimination in people with mild AD, versus Caretakers. METHODS: Twenty AD subjects and 22 caretakers underwent computerized testing of emotion recognition and differentiation. Performances between groups were compared, controlling for possible effects of age and cognitive abilities. RESULTS: AD subjects showed diminished recognition of happy, sad, fearful, and neutral expressions. They also exhibited decreased differentiation between happy and sad expressions. Controlling for effects of cognitive dysfunction, AD subjects differed on recognition of happy and sad, and differentiation of sad facial expressions, and in error patterns for fearful and neutral faces. CONCLUSIONS: Diminished abilities for emotion discrimination are present in persons with mild AD. In persons with mild AD, who frequently reside in their own home or with close family, this diminished ability may adversely affect social functioning and quality of life.

Aged↗

Differences in facial expressions of four universal emotions.

The facial action coding system (FACS) was used to examine recognition rates in 105 healthy young men and women who viewed 128 facial expressions of posed and evoked happy, sad, angry and fearful emotions in color photographs balanced for gender and ethnicity of poser. Categorical analyses determined the specificity of individual action units for each emotion. Relationships between recognition rates for different emotions and action units were evaluated using a logistic regression model. Each emotion could be identified by a group of action units, characteristic to the emotion and distinct from other emotions. Characteristic happy expressions comprised raised inner eyebrows, tightened lower eyelid, raised cheeks, upper lip raised and lip corners turned upward. Recognition of happy faces was associated with cheek raise, lid tightening and outer brow raise. Characteristic sad expressions comprised furrowed eyebrow, opened mouth with upper lip being raised, lip corners stretched and turned down, and chin pulled up. Only brow lower and chin raise were associated with sad recognition. Characteristic anger expressions comprised lowered eyebrows, eyes wide open with tightened lower lid, lips exposing teeth and stretched lip corners. Recognition of angry faces was associated with lowered eyebrows, upper lid raise and lower lip depression. Characteristic fear expressions comprised eyes wide open, furrowed and raised eyebrows and stretched mouth. Recognition of fearful faces was most highly associated with upper lip raise and nostril dilation, although both occurred infrequently, and with inner brow raise and widened eyes. Comparisons are made with previous studies that used different facial stimuli.

Adolescent↗

Symptom and demographic profiles in first-episode schizophrenia.

First-episode schizophrenia (FE-SZP) presents a diagnostic challenge because of symptomatic overlap between the various causes of psychosis. An early and accurate diagnosis is important for the implementation of appropriate treatment, for determining prognosis and for identifying research participants. In an effort to facilitate early diagnosis, we followed a group of first-episode psychosis patients with a presumptive diagnosis of schizophrenia who were subsequently diagnosed at 6-month follow-up with either schizophrenia (n=104) or other psychiatric diagnoses (n=19). The two groups-first-episode schizophrenia and first-episode non-schizophrenia-were compared on measures of demographics, symptoms, quality of life, premorbid adjustment and lateral dominance. Odds ratios were calculated for each variable and all significant variables were entered into a multivariate prediction model. The model showed that higher levels of anhedonia and hallucinations increased the odds of a final diagnosis of schizophrenia. This predictive model was validated in a smaller group of patients.

Adolescent↗

Recognition of facial emotions in neuropsychiatric disorders.

Recognition of facial emotions represents an important aspect of interpersonal communication and is governed by select neural substrates. We present data on emotion recognition in healthy young adults utilizing a novel set of color photographs of evoked universal emotions. In addition, we review the recent literature on emotion recognition in psychiatric and neurologic disorders, and studies that compare different disorders.

Affect↗

Patient attitudes towards surgically implantable, long-term delivery of psychiatric medicine.

The introduction of surgically implantable medication delivery systems provides psychiatric patients with reversible, uninterrupted access to medication for up to 14 months. This study designed and administered a survey to assess patients' attitudes and beliefs towards illness, medication, and this potential new treatment method. The survey included questions about demographics, insight and attitudes towards illness, current and past medication adherence, attitudes towards psychiatric and nonpsychiatric medications, and understanding and attitudes towards surgical implants. The sample of 206 psychiatric patients was almost equally split between favorably and unfavorably considering implants. Patients favorable towards implants ascribed forgetting and failure to refill medication on time as the reasons for missing doses, recognized the benefits of medication in general, and understood that the implant would be inserted under the skin. Favorable consideration of implants was positively correlated with the desire to avoid adverse consequences of missing medicine, stay well, avoid the need for daily oral medications, and decrease family burden. Unfavorable consideration of implants was related to a preference to take medication orally, concern about feeling controlled, unwillingness to try something new, and not understanding that the implant would be placed under the skin. Demographic variables, past/current medications, specific diagnosis, and illness severity did not influence the decision. This survey elucidates patients' attitudes and beliefs towards illness, medication, and surgical implants. The results indicate that a significant proportion of patients recognize the difficulties of medication adherence and the need for better methods to attain therapeutic response. Thus, the study provides impetus for future work in this area.

Adult↗

Facial emotion recognition in schizophrenia: intensity effects and error pattern.

OBJECTIVE: The authors used color photographs of emotional and neutral expressions to investigate recognition patterns of five universal emotions in schizophrenia. METHOD: Twenty-eight stable outpatients with schizophrenia (19 men and nine women) and 61 healthy subjects (29 men and 32 women) completed an emotion discrimination test that presented mild and extreme intensities of happy, sad, angry, fearful, disgusted, and neutral faces, balanced for gender and ethnicity. Analyses evaluated accuracy of identifying emotions as a function of intensity, diagnosis, and gender of poser and rater. RESULTS: Patients performed worse than comparison subjects on recognition of all emotions and neutral faces combined, including mild and extreme expressions. For specific emotions, patients performed worse on recognition of fearful, disgusted, and neutral expressions. For all emotions except disgust, recognition of extreme intensity was better than recognition of mild intensity. However, patients showed less benefit from increased intensity for all emotions combined, and the difference was most pronounced for fear. Thus, patients were more impaired than healthy comparison subjects in identifying high-intensity expressions, even though this was an easier task than identifying low-intensity expressions. In the comparison of patterns of errors, patients and healthy subjects differed only in misattributions of neutral expressions; patients overattributed disgusted expressions and underattributed happy expressions. CONCLUSIONS: Patients with schizophrenia were impaired in overall emotion recognition, particularly fear and disgust, and did not benefit from increased emotional intensity. Error patterns indicate that patients misidentified neutral cues as negatively valenced.

Adult↗

Postpsychotic depression in schizophrenia patients.

Depression is a frequent comorbidity in the course of schizophrenia and is associated with increased mortality from suicide. Postpsychotic depression is defined as the syndrome of major depression occurring following remission of psychotic symptoms in a person with schizophrenia. Various proposed causes, differential diagnosis, and issues regarding management of postpsychotic depression are discussed.

Major Depressive Disorder↗